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Identification
Name Daclizumab
Accession Number DB00111 (BIOD00007, BTD00007)
Type biotech
Groups approved
Description

Humanized IgG1 Mab that binds to the human interleukin-2 receptor (anti-Tac or anti-CD25). Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. The human sequences were derived from the constant domains of human IgG1 and the variable framework regions of the Eu myeloma antibody. The murine sequences were derived from the complementarity-determining regions of a murine anti-Tac antibody.
Protein structure Db00111
Display: 3D Structure
Protein chemical formula C6332H9808N1678O1989S42
Protein average weight 142612.1000
Sequences 
>Humanized Anti-CD25 Heavy Chain 1
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEY
NQKFKDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSSGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
VTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGK

>Humanized Anti-CD25 Light Chain 1
DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPAR
FSGSGSGTEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNR

>Humanized Anti-CD25 Heavy Chain 2
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSYRMHWVRQAPGQGLEWIGYINPSTGYTEY
NQKFKDKATITADESTNTAYMELSSLRSEDTAVYYCARGGGVFDYWGQGTTLTVSSGPSV
FPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV
VTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSVFLFPP
KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL
TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC
SVMHEALHNHYTQKSLSLSPGK

>Humanized Anti-CD25 Light Chain 2
DIQMTQSPSTLSASVGDRVTITCSASSSISYMHWYQQKPGKAPKLLIYTTSNLASGVPAR
FSGSGSGTEFTLTISSLQPDDFATYYCHQRSTYPLTFGSGTKVEVKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNR

FASTA
Synonyms
Anti-IL-2
Humanized antiCD25
Ig gamma-1 chain C region
Salts Not Available
Brand names
Name Company
Zenapax (Hoffmann-La Roche Inc)
Brand mixtures Not Available
Categories
  • Immunomodulatory Agents
  • Immunosuppressive Agents
CAS number 152923-56-3
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication Zenapax is a humanized monoclonal antibody used for prevention of renal transplant rejection
Pharmacodynamics Zenapax functions as an IL-2 receptor antagonist. Specifically it inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.
Mechanism of action Zenepax binds with high-affinity to the Tac subunit of the high-affinity IL-2 receptor complex and inhibits IL-2 binding. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Most likely removed by opsonization via the reticuloendothelial system when bound to lymphocytes.
Route of elimination Not Available
Half life 11-38 days
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices Not Available
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
melting point 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity -0.437 Not Available
isoelectric point 8.46 Not Available
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
UniProt P01857 Link_out
Genbank J00228 Link_out
PharmGKB PA164764446 Link_out
Drug Product Database 2241473 Link_out
RxList http://www.rxlist.com/cgi/generic3/zenapax.htm Link_out
Drugs.com http://www.drugs.com/cdi/daclizumab.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Daclizumab Link_out
ATC Codes
  • L04AC01
AHFS Codes
  • 92:00.00
PDB Entries
FDA label show (666 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available
Targets

1. Interleukin-2 receptor alpha chain

Pharmacological action: yes
Actions: antibody

Receptor for interleukin-2

Organism class: human
UniProt ID: P01589 Link_out
Gene: IL2RA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Shamsi TS, Irfan M, Farzana T, Ansari SH, Ahmad G, Shakoor N, Baig MI: Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor antibody Daclizumab for the prevention of acute graft versus host disease in steroid refractory Diamond Blackfan anaemia: a case report. J Pak Med Assoc. 2005 Oct;55(10):454-5. Pubmed
  2. Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I, Lu JG, Gajewski J, Durett A, Cleary K, Champlin R, Andersson BS, Light S: Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000 Jan 1;95(1):83-9. Pubmed
  3. Garcia CD, Bittencourt VB, Tumelero A, Antonello JS, Malheiros D, Garcia VD: Plasmapheresis for recurrent posttransplant focal segmental glomerulosclerosis. Transplant Proc. 2006 Jul-Aug;38(6):1904-5. Pubmed
  4. Krouwels FH, van der Heijden JF, Lutter R, van Neerven RJ, Jansen HM, Out TA: Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. Am J Respir Cell Mol Biol. 1996 Apr;14(4):388-97. Pubmed
  5. Patlolla V, Zhong X, Reed GW, Mandelbrot DA: Efficacy of anti-IL-2 receptor antibodies compared to no induction and to antilymphocyte antibodies in renal transplantation. Am J Transplant. 2007 Jul;7(7):1832-42. Pubmed
  6. Monti P, Brigatti C, Heninger AK, Scirpoli M, Bonifacio E: Disengaging the IL-2 receptor with daclizumab enhances IL-7-mediated proliferation of CD4 and CD8 T cells. Am J Transplant. 2009 Dec;9(12):2727-35. Epub 2009 Sep 25. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Interleukin-2 receptor subunit beta

Pharmacological action: yes
Actions: antibody

Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2

Organism class: human
UniProt ID: P14784 Link_out
Gene: IL2RB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Light JA, Sasaki TM, Ghasemian R, Barhyte DY, Fowlkes DL: Daclizumab induction/tacrolimus sparing: a randomized prospective trial in renal transplantation. Clin Transplant. 2002;16 Suppl 7:30-3. Pubmed
  2. Aguillon JC, Contreras J, Dotte A, Cruzat A, Catalan D, Salazar L, Molina MC, Guerrero J, Lopez M, Soto L, Salazar-Onfray F, Cuchacovich M: [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies] Rev Med Chil. 2003 Dec;131(12):1445-53. Pubmed
  3. Forrest K, Logan B, Strange J, Roszman TL, Goebel J: Daclizumab therapy in kidney transplantation-different mechanisms of action in- versus ex-vivo? Transpl Immunol. 2005 Mar;14(1):43-7. Epub 2005 Jan 4. Pubmed
  4. Ramos EL, Milford EL, Kirkman RL, Tilney NL, Strom TB, Shapiro ME, Waldmann TA, Wood IG, Rollins MR, Carpenter CB: Differential IL-2 receptor expression in renal allograft recipients treated with an anti-IL-2-receptor antibody. Transplantation. 1989 Sep;48(3):415-20. Pubmed
  5. Burkhardt K, Mandel TE, Diamantstein T, Loughnan MS: Anti-IL-2 receptor monoclonal antibody AMT-13 increases soluble IL-2 receptor levels in vivo. Immunology. 1989 Feb;66(2):183-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Low affinity immunoglobulin gamma Fc region receptor III-B

Pharmacological action: unknown

Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils

Organism class: human
UniProt ID: O75015 Link_out
Gene: FCGR3B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hoshino S, Oshimi K, Teramura M, Mizoguchi H: Activation via the CD3 and CD16 pathway mediates interleukin-2-dependent autocrine proliferation of granular lymphocytes in patients with granular lymphocyte proliferative disorders. Blood. 1991 Dec 15;78(12):3232-40. Pubmed
  2. Martelletti P, Stirparo G, De Stefano L, Di Sabato F, Giacovazzo M, Rinaldi-Garaci C: Defective expression of IL-2 receptors on peripheral blood lymphocytes from patients with cluster headache. Headache. 1990 Mar;30(4):228-31. Pubmed
  3. Galandrini R, Albi N, Tripodi G, Zarcone D, Terenzi A, Moretta A, Grossi CE, Velardi A: Antibodies to CD44 trigger effector functions of human T cell clones. J Immunol. 1993 May 15;150(10):4225-35. Pubmed
  4. Lanier LL, Kipps TJ, Phillips JH: Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med. 1985 Dec 1;162(6):2089-106. Pubmed
  5. Hayakawa K, Salmeron MA, Kornbluth J, Bucana C, Itoh K: The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4-dependent versus an IL-2-dependent natural killer cell clone. J Immunol. 1991 Apr 1;146(7):2453-60. Pubmed

4. Complement C1r subcomponent

Pharmacological action: unknown

C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system

Organism class: human
UniProt ID: P00736 Link_out
Gene: C1R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

5. Complement C1q subcomponent subunit A

Pharmacological action: unknown

C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes

Organism class: human
UniProt ID: P02745 Link_out
Gene: C1QA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

6. Complement C1q subcomponent subunit B

Pharmacological action: unknown

C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes

Organism class: human
UniProt ID: P02746 Link_out
Gene: C1QB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Complement C1q subcomponent subunit C

Pharmacological action: unknown

C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes

Organism class: human
UniProt ID: P02747 Link_out
Gene: C1QC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

8. Low affinity immunoglobulin gamma Fc region receptor III-A

Pharmacological action: unknown

Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis

Organism class: human
UniProt ID: P08637 Link_out
Gene: FCGR3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

9. High affinity immunoglobulin gamma Fc receptor I

Pharmacological action: unknown

Binds to the Fc region of immunoglobulins gamma. High affinity receptor

Organism class: human
UniProt ID: P12314 Link_out
Gene: FCGR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Simms HH, Gaither TA, Fries LF, Frank MM: Monokines released during short-term Fc gamma receptor phagocytosis up-regulate polymorphonuclear leukocytes and monocyte-phagocytic function. J Immunol. 1991 Jul 1;147(1):265-72. Pubmed

10. Low affinity immunoglobulin gamma Fc region receptor II-a

Pharmacological action: unknown

Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens

Organism class: human
UniProt ID: P12318 Link_out
Gene: FCGR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

11. Low affinity immunoglobulin gamma Fc region receptor II-b

Pharmacological action: unknown

Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B- cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis

Organism class: human
UniProt ID: P31994 Link_out
Gene: FCGR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

12. Low affinity immunoglobulin gamma Fc region receptor II-c

Pharmacological action: unknown

Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells

Organism class: human
UniProt ID: P31995 Link_out
Gene: FCGR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on June 14, 2012 13:56